Atomic Local Neighborhood Flexibility Incorporation into a Structured Similarity Measure for QSAR
Atomic Local Neighborhood Flexibility Incorporation into a Structured Similarity Measure for QSAR
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DOI：
10.1021/ci800329r
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发表时间：
2009-03-01
影响因子：
5.6
通讯作者：
Zell, Andreas
中科院分区：
文献类型：
--
作者：
Fechner, Nikolas;Jahn, Andreas;Zell, Andreas
在这项工作中，我们介绍了一种新的方法，通过近似构象空间或分子来考虑结构相似性度量中的几何。我们的想法是将分子构象分解成邻近原子相对于核心原子的局部构象。这种局部几何形状可以通过相邻原子的轨迹隐含地访问，这些原子通过可旋转的键出现。在我们的方法中，可以用于结构相似性度量的物理化学原子相似性被局部柔性相似性所增强，局部柔性相似性给出了局部构象空间的相似性的粗略估计。我们将这种编码灵活性的新类型引入到最优分配分子相似度方法中，该方法可以作为支持向量机的伪核。在几个已发表的QSAR数据集上对局部灵活性的影响进行了评估。与未修改的最优分配核相比，这导致了10个数据集中有9个的模型质量得到了改善。
In this work, we introduce a new method to regard the geometry in a structural similarity measure by approximating the conformational space or a molecule. Our idea is to break down the molecular conformation into the local conformations of neighbor atoms with respect to core atoms. This local geometry can be implicitly accessed by the trajectories of the neighboring atoms, which are emerge by rotatable bonds. In our approach, the physicochemical atomic similarity, which can be used in structured similarity measures, is augmented by a local flexibility similarity, which gives a rough estimate of the similarity of the local conformational space. We incorporated this new type of encoding the flexibility into the optimal assignment molecular similarity approach, which can be used as a pseudokernel in support vector machines. The impact of the local flexibility was evaluated on several published QSAR data sets. This lead to an improvement of the model quality on 9 out of 10 data sets compared to the unmodified optimal assignment kernel.